Neutralizing Antibodies and Cytokines in Breast Milk After Coronavirus Disease 2019 (COVID-19) mRNA Vaccination

  1. Vignesh Narayanaswamy
  2. Brian T. Pentecost
  3. Corina N. Schoen
  4. Dominique Alfandari
  5. Sallie S. Schneider
  6. Ryan Baker
  7. Kathleen F. Arcaro

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Abstract

To evaluate immune responses to coronavirus disease 2019 (COVID-19) mRNA-based vaccines present in breast milk and transfer of the immune responses to breastfeeding infants.

METHODS:

We enrolled 30 lactating women who received mRNA-based COVID-19 vaccines from January through April 2021 in this cohort study. Women provided serial milk samples, including milk expressed before vaccination, across 2–3 weeks after the first dose, and across 3 weeks after the second dose. Women provided their blood, spotted on cards (dried blood spots), 19 days after the first dose and 21 days after the second dose. Stool samples from the breastfed infants were collected 21 days after mothers' second vaccination. Prepandemic samples of milk, dried blood spots, and infant stool were used as controls. Milk, dried blood spots, and infant stool were tested by enzyme-linked immunosorbent assay for receptor-binding domain (RBD)–specific immunoglobulin (Ig)A and IgG. Milk samples were tested for the presence of neutralizing antibodies against the spike and four variants of concern: D614G, Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1). Levels of 10 cytokines were measured in milk samples.

RESULTS:

Milk from COVID-19-immunized women neutralized the spike and four variants of concern, primarily driven by anti-RBD IgG. The immune response in milk also included significant elevation of interferon-γ. The immune response to maternal vaccination was reflected in breastfed infants: anti-RBD IgG and anti-RBD IgA were detected in 33% and 30% of infant stool samples, respectively. Levels of anti-RBD antibodies in infant stool correlated with maternal vaccine side effects. Median antibody levels against RBD were below the positive cutoffs in prepandemic milk and infant stool samples.

CONCLUSION:

Humoral and cellular immune responses to mRNA-based COVID-19 vaccination are present in most women’s breast milk. The milk anti-RBD antibodies can neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike and variants of concern. Anti-RBD antibodies are transferred to breastfed infants, with the potential to confer passive immunity against SARS-CoV-2.

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  1. Version published to 10.1097/aog.0000000000004661
  2. ScreenIT

    SciScore for 10.1101/2021.10.12.21264890: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: A total of 30 women were enrolled in the study and provided consent under UMass Amherst IRB-approved protocol #2534.
    Field Sample Permit: Pre-pandemic milk, maternal DBS, and infant stool samples were collected using the same methods as samples in the vaccine cohort (see Sample collection).
    Sex as a biological variableA total of 30 women were enrolled in the study and provided consent under UMass Amherst IRB-approved protocol #2534.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    For detection of total immunoglobulins, 96-well plates were coated with anti-IgA (α-chain specific) or anti-IgG (H+L specific) capture antibodies at 1 μg/mL (Jackson ImmunoResearch Laboratories, Inc.).
    anti-IgA
    suggested: None
    α-chain
    suggested: None
    anti-IgG
    suggested: None
    The assay quantitatively measures antibodies in the sample that can inhibit the interaction of spike and its variants with ACE2.
    ACE2
    suggested: None
    Independent t-tests were used to analyze differences in infant stool anti-RBD antibodies, stratified by the presence of maternal side effects to immunization.
    anti-RBD
    suggested: None
    Software and Algorithms
    SentencesResources
    Information was logged via Research Electronic Data Capture (REDCap).
    REDCap
    suggested: (REDCap, RRID:SCR_003445)
    Infant stool samples were collected in stool collection tubes (Fisher Sci., Cat No. NC0705093)
    Fisher Sci.
    suggested: (One Mind Biospecimen Bank Listing, RRID:SCR_004193)
    Statistical analyses were performed using GraphPad Prism 9.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.10.12.21264890v1 on medRxiv